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Hypothermia for Traumatic Brain Injury in Children

Not effective and possibly harmful

Animal models and small studies in children and adults suggest a benefit for hypothermia therapy in the treatment of severe traumatic brain injury. In an international trial, researchers compared outcomes in children (age range, 1–17 years) with traumatic brain injury who were randomized to either hypothermia therapy for 24 hours (32.0°C–33.0°C) or normothermia (36.5°C–37.5°C). Eligible patients had Glasgow Coma Scale scores 8 at the scene or in the emergency department, needed mechanical ventilation, and had evidence of acute brain injury on computed tomography scan. Patients who were screened more than 8 hours after injury or who had refractory shock, nonaccidental injury, high cervical spinal cord injury, or acute isolated epidural hematoma were excluded.

Of 1441 patients who were screened during more than 5 years, 327 met eligibility criteria and 225 were enrolled. Complete data were available for 91% of enrolled patients. Mean time from injury to initiation of cooling was 6.3 hours, and mean time to achieve hypothermia was 3.9 hours. Significantly more patients in the hypothermia group than in the normothermia group received vasoactive drugs for hypotension, usually during the rewarming period.

The proportion of patients with an unfavorable outcome — defined as severe disability, death, or persistent vegetative state at 6 months (the primary outcome) — was 31% in the hypothermia group and 22% in the normothermia group, a nonsignificant difference (relative risk for an unfavorable outcome with hypothermia therapy, 1.41). After adjustment for clinical factors that might be associated with an unfavorable outcome, the odds ratio for an unfavorable outcome with hypothermia therapy was 2.33. Death rates did not differ significantly between the hypothermia and normothermia groups (21% vs. 12%). No evidence of benefit was detected in analyses of any of eight subgroups, including patients who were treated early.

Comment: This study was remarkably ambitious, given the low incidence of eligible patients (5 per month in 17 pediatric hospitals in 3 countries). Despite this obstacle, the researchers showed unequivocally that hypothermia has no benefit. Although a greater proportion of children who were treated with hypothermia than with normothermia had poor outcomes, the difference did not reach statistical significance. Induced hypothermia is not indicated for treatment of acute severe brain injury in children.

— J. Stephen Bohan, MD, MS, FACP, FACEP

Published in Journal Watch Emergency Medicine June 4, 2008

Citation(s):

Hutchison JS et al. Hypothermia therapy after traumatic brain injury in children. N Engl J Med 2008 Jun 5; 358:2447.

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